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PD-L1 presenting platelets reverse new-onset type 1 diabetes

A technology of PD-L1 and platelets, applied in the direction of retroRNA virus, resistance to vector-borne diseases, viruses, etc., can solve problems such as adverse reactions and safety

Pending Publication Date: 2021-07-23
NORTH CAROLINA STATE UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Although anti-CD3 antibodies can reverse new-onset T1D, this antigen-

Method used

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  • PD-L1 presenting platelets reverse new-onset type 1 diabetes
  • PD-L1 presenting platelets reverse new-onset type 1 diabetes
  • PD-L1 presenting platelets reverse new-onset type 1 diabetes

Examples

Experimental program
Comparison scheme
Effect test

example 1

[0072] a) Results

[0073] (1) Establish a megakaryocyte (MK) cell line stably expressing PD-L1.

[0074] Platelets are initially released into the blood from mature MK residing in the bone marrow. For the generation of platelets in vitro, the murine MK progenitor cell line L8057 was used. L8057 cells undergo a process of maturation, differentiation and platelet release after stimulation with 12-myristate 13-phorbol acetate (PMA). To genetically engineer L8057 cells stably expressing PD-L1, L8057 cells were infected with a lentivirus encoding murine PD-L1. Subsequently, infected cells were selected with puromycin to obtain stable cell lines. EGFP-PD-L1 was overexpressed and localized on the cell membrane of L8057 cells as shown by the cell membrane dye Alexa Fluor 594-conjugated wheat germ agglutinin (WGA594) (Fig. 1b). The expression of EGFP-PD-L1 in L8057 cells was further detected by Western blotting (Fig. 1c). Furthermore, the MK cell marker CD41a was detected on EGFP...

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Abstract

The invention discloses a therapeutic agent delivery menstruum comprising a modified platelet comprising a therapeutic agent cargo and a targeting moiety and methods for treating diabetes, autoinflammatory disease, and/or graft-versus-host disease comprising administering the same to a subject.

Description

[0001] This application claims the benefit of U.S. Provisional Application No. 62 / 743,857, filed October 10, 2018, which is incorporated herein by reference in its entirety. Background technique [0002] Type 1 diabetes (T1D) results from dysregulation of the immune system due to genetic predisposition, environmental factors, and pathophysiology. Autoreactive lymphocytes destroy insulin-producing beta-cells, resulting in insufficient insulin production and leading to uncontrolled blood sugar levels and multiple types of secondary complications. Infiltration of various types of lymphocytes has been detected in the pancreas of T1D patients. Among these pancreas-infiltrating lymphocytes, islet-antigen-reactive T cells play a major role in disease initiation and progression. These T cells can destroy β-cells through T cell receptor (TCR)-mediated cytotoxicity and production of cytokines such as interferon-γ (IFN-γ). Due to the central role of autoreactive lymphocytes in the path...

Claims

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Application Information

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IPC IPC(8): A61K35/19A61K39/00A61K47/69A61P3/10A61P37/06C07K14/705C12N5/00C12N15/85
CPCA61K35/19A61P3/10A61P37/06A61K47/6901A61K39/0008A61K2039/6056C12N5/0644C12N2510/00C07K14/70532C07K14/70575Y02A50/30C12N2740/16043
Inventor 顾臻王金强张旭东
Owner NORTH CAROLINA STATE UNIV
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